PUBLICATION

M. fortuitum-induced CNS-pathology: Deciphering the role of canonical Wnt signaling, blood brain barrier components and cytokines

Authors
Sharma, S., Kumar, M., Kumar, J., Srivastava, N., Hussain, M.A., Shelly, A., Mazumder, S.
ID
ZDB-PUB-210504-2
Date
2021
Source
Developmental and comparative immunology   122: 104111 (Journal)
Registered Authors
Keywords
CNS-pathology, Cytokines, Mycobacterium fortuitum, Wnt-signaling, Zebrafish
MeSH Terms
  • Axin Protein/metabolism
  • Cytokines/metabolism*
  • Brain/microbiology
  • Brain/pathology*
  • Interferon-gamma/immunology
  • Th2 Cells/immunology
  • Interleukin-4/immunology
  • Th1 Cells/immunology
  • Wnt Proteins/metabolism
  • Adherens Junctions/genetics
  • Blood-Brain Barrier/metabolism
  • Blood-Brain Barrier/microbiology*
  • Mycobacterium fortuitum/immunology*
  • Mycobacterium fortuitum/pathogenicity
  • Calpain/metabolism
  • Interleukin-10/immunology
  • Wnt3A Protein/metabolism
  • Zebrafish/immunology*
  • Zebrafish/microbiology
  • Wnt Signaling Pathway/immunology*
  • Mycobacterium Infections, Nontuberculous/pathology
  • Mycobacterium Infections, Nontuberculous/veterinary
  • Receptors, Cell Surface/metabolism
  • Zebrafish Proteins/metabolism
  • Glycogen Synthase Kinase 3 beta/metabolism
  • Animals
  • Fish Diseases/immunology*
  • Fish Diseases/microbiology
  • Tight Junctions/genetics
  • beta Catenin/metabolism
  • Tumor Necrosis Factor-alpha/immunology
  • Low Density Lipoprotein Receptor-Related Protein-6/metabolism
  • Low Density Lipoprotein Receptor-Related Protein-5/metabolism
(all 33)
PubMed
33933535 Full text @ Dev. Comp. Immunol.
Abstract
Molecular underpinning of mycobacteria-induced CNS-pathology is not well understood. In the present study, zebrafish were infected with Mycobacterium fortuitum and the prognosis of CNS-pathogenesis studied. We observed M. fortuitum triggers extensive brain-pathology. Evans blue extravasation demonstrated compromised blood-brain barrier (BBB) integrity. Further, decreased expression in tight-junction (TJ) and adherens junction complex (AJC) genes were noted in infected brain. Wnt-signaling has emerged as a major player in host-mycobacterial immunity but its involvement/role in brain-infection is not well studied. Sustained expression of wnt2, wnt3a, fzd5, lrp5/6 and β-catenin, with concordant decline in degradation complex components axin, gsk3β and β-catenin regulator capn2a were observed. The surge in ifng1 and tnfa expression preceding il10 and il4 suggested cytokine-interplay critical in M. fortuitum-induced brain-pathology. Therefore, we suggest adult zebrafish as a viable model for studying CNS-pathology and using the same, conclude that M. fortuitum infection is associated with repressed TJ-AJC gene expression and compromised BBB permeability. Our results implicate Wnt/β-catenin pathway in M. fortuitum-induced CNS-pathology wherein Th1-type signals facilitate bacterial clearance and Th2-type signals prevent the disease sequel.
Genes / Markers
Figures
No images available
Expression
Phenotype
No data available
Mutations / Transgenics
No data available
Human Disease / Model
No data available
Sequence Targeting Reagents
No data available
Fish
No data available
Antibodies
No data available
Orthology
Engineered Foreign Genes
No data available
Mapping
Your Input Welcome
We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
Citation
Sharma, S., Kumar, M., Kumar, J., Srivastava, N., Hussain, M.A., Shelly, A., Mazumder, S. (2021) M. fortuitum-induced CNS-pathology: Deciphering the role of canonical Wnt signaling, blood brain barrier components and cytokines. Developmental and comparative immunology. 122:104111.